Core B, the Antibody / Ig Fusion Core, provides an important means by which the PPG will achieve its goals of understanding the immune response in tolerance, autoimmunity and infection. Core B will coordinate the use of mAb and Ig fusion proteins to enable the study of the roles of the PD-1 and other coinhibitory pathways in regulating immune responses during acute and chronic infection, chronic graft versus host disease (cGVHD), and autoimmunity. To achieve these goals Core B has the following aims:
Aim 1 : To maintain and produce existing and newly generated mAbs and Ig fusion proteins for PPG investigators. An extensive set of mAbs and fusion proteins against coinhibitory molecules has been generated in the first cycle of this PPG and these will continue to be produced as well as characterized for additional activities.
Aim 2 : To generate novel monoclonal antibodies and Ig fusion proteins to study the function and expression of coinhibitory receptors and ligands. RGMb and PROCR are newly identified co-inhibitory molecules that impact T cell exhaustion and the PD-1 pathway. Core B will generate novel antibodies that will facilitate analysis of the function and expression of coinhibitory molecules particularly PD-1/PD-L, RGMb, and PROCR pathway members as well as other coinhibitory pathways. These include novel mouse anti-mouse antibodies made in knockout mice that see novel epitopes including anti-PD-1, PD-L1, PD-L2 for long-term treatment of mice without anti-antibody responses. These novel mouse anti-mouse mAbs will also be made as recombinant mAbs with mutated Fc to eliminate effects due to cell depletion or FcR signaling. This best models PD-1 mAbs used in clinical trials. Core B will generate novel multimeric Ig fusion proteins of these coinhibitory pathway proteins in order to either block or transduce signals via cross-linking receptors. The production of these critical reagents by a core not only will be time and cost efficient, but also provide standardized reagents that will facilitate comparison of data by investigators in this PPG. Core B will work closely with all PPG investigators, providing mAbs and Ig fusion proteins and identifying new needs. These reagents will allow PPG investigators to develop a comprehensive understanding of the roles of positive and negative second signals in modulating T cell activation, tolerance and exhaustion. The production of these critical reagents by a core not only will be time and cost efficient, but also provide standardized reagents that will facilitate comparison of data by investigators in this PPG.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard Medical School
United States
Zip Code
Blazar, Bruce R; MacDonald, Kelli P A; Hill, Geoffrey R (2018) Immune regulatory cell infusion for graft-versus-host disease prevention and therapy. Blood 131:2651-2660
Chihara, Norio; Madi, Asaf; Kondo, Takaaki et al. (2018) Induction and transcriptional regulation of the co-inhibitory gene module in T cells. Nature 558:454-459
Sage, Peter T; Schildberg, Frank A; Sobel, Raymond A et al. (2018) Dendritic Cell PD-L1 Limits Autoimmunity and Follicular T Cell Differentiation and Function. J Immunol 200:2592-2602
Lu, Yunjie; Gao, Ji; Zhang, Shaopeng et al. (2018) miR-142-3p regulates autophagy by targeting ATG16L1 in thymic-derived regulatory T cell (tTreg). Cell Death Dis 9:290
Dixon, Karen O; Schorer, Michelle; Nevin, James et al. (2018) Functional Anti-TIGIT Antibodies Regulate Development of Autoimmunity and Antitumor Immunity. J Immunol 200:3000-3007
Fan, Martin Y; Turka, Laurence A (2018) Immunometabolism and PI(3)K Signaling As a Link between IL-2, Foxp3 Expression, and Suppressor Function in Regulatory T Cells. Front Immunol 9:69
Wu, Chuan; Chen, Zuojia; Xiao, Sheng et al. (2018) SGK1 Governs the Reciprocal Development of Th17 and Regulatory T Cells. Cell Rep 22:653-665
Juchem, Kathryn W; Sacirbegovic, Faruk; Zhang, Cuiling et al. (2018) PD-L1 Prevents the Development of Autoimmune Heart Disease in Graft-versus-Host Disease. J Immunol 200:834-846
Priyadharshini, Bhavana; Loschi, Michael; Newton, Ryan H et al. (2018) Cutting Edge: TGF-? and Phosphatidylinositol 3-Kinase Signals Modulate Distinct Metabolism of Regulatory T Cell Subsets. J Immunol 201:2215-2219
Porichis, Filippos; Hart, Meghan G; Massa, Alexandra et al. (2018) Immune Checkpoint Blockade Restores HIV-Specific CD4 T Cell Help for NK Cells. J Immunol 201:971-981

Showing the most recent 10 out of 332 publications